Highlighted research articles
Journal: Cancer Discovery (2023)

In This Issue| August 04 2023 Highlighted research articles Author & Article Information Online ISSN: 2159-8290 Print ISSN: 2159-8274 ©2023 American Association for Cancer Research2023American Association for Cancer Research Cancer Discov (2023) 13 (8): 1749–1751. https://doi.org/10.1158/2159-8290.CD-13-8-ITI Related Content This is a related article to: Effectors Enabling Adaptation to Mitochondrial Complex I Loss in Hürthle Cell Carcinoma This is a related article to: Distinct Assemblies of Heterodimeric Cytokine Receptors Govern Stemness Programs in Leukemia This is a related article to: SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy View more This is a related article to: Spatial Transcriptomics of Intraductal Papillary Mucinous Neoplasms of the Pancreas Identifies NKX6-2 as a Driver of Gastric Differentiation and Indolent Biological Potential This is a related article to: Mitochondrial-Encoded Complex I Impairment Induces a Targetable Dependency on Aerobic Fermentation in Hürthle Cell Carcinoma of the Thyroid This is a related article to: Targeting N-linked Glycosylation for the Therapy of Aggressive Lymphomas This is a related article to: The MDM2–p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced or Metastatic Solid Tumors: Results of a Phase Ia, First-in-Human, Dose-Escalation Study This is a related article to: Spectrum of Response to Platinum and PARP Inhibitors in Germline BRCA–Associated Pancreatic Cancer in the Clinical and Preclinical Setting This is a related article to: Clinical Activity and Exploratory Resistance Mechanism of Milademetan, an MDM2 Inhibitor, in Intimal Sarcoma with MDM2 Amplification: An Open-Label Phase Ib/II Study View less Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record August 4 2023 Citation Highlighted research articles. Cancer Discov 1 August 2023; 13 (8): 1749–1751. https://doi.org/10.1158/2159-8290.CD-13-8-ITI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Targeted therapy combinations are poised to transform cancer care, but traditional phase I trial designs make exploration difficult in early clinical development. After preclinically demonstrating that the novel SHP2 inhibitor PF-07284892 (ARRY-558) overcomes resistance to diverse targeted therapies, Drilon and colleagues used an alternative dose-escalation design in a phase I trial, allowing for oncogene-matched targeted therapy addition after a SHP2 inhibitor monotherapy lead-in period. In targeted therapy–resistant oncogene-driven cancers treated at dose level one, combination therapy led to rapid tumor and circulating tumor DNA reduction, providing proof of concept for an efficient and patient-centric paradigm for investigating novel–known drug combinations. See article, p. 1789. Dysregulation of MDM2 is one mechanism of inactivating wild-type TP53 in cancer and frequently occurs through gene amplifications. Attempts to inhibit MDM2 and indirectly reactivate p53 in clinical trials have been hampered by dose-limiting myelosuppression. In this study, LoRusso and colleagues report on a phase... You do not currently have access to this content.